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HbeAg negative and DNA Hbsag quant question
I'm hoping to get some help understanding something that totally confuses me. For those of us that are HbeAg negative and NOT on antivirals.....why do some have high DNA but very low hbsag and others have low/undetectable DNA but high hbsag?
thank you for your response. always great to have someone on the forum that we can learn so much from.
I don't think the guidelines will change in light of these arrowhead results.
this is all kind of new to the hepatologists community and the consequences, while logic, have not been shown in analytical trial fashion.
Many e ag pos patients are in the immuntolerant phase, with normal alt and no measurable liver damage. Treating those is not a popular idea at this time, in particular since an hbsag seroconversion is quite unlikely from this condition without immune activation and interferon is not effective in those patients.
this is all kind of new to the hepatologists community and the consequences, while logic, have not been shown in analytical trial fashion.
Many e ag pos patients are in the immuntolerant phase, with normal alt and no measurable liver damage. Treating those is not a popular idea at this time, in particular since an hbsag seroconversion is quite unlikely from this condition without immune activation and interferon is not effective in those patients.
My case is somewhat similar to the topic of discussion going on here...and I'm bit confused...
My results are :-
HbsAg + (reactive)
HbeAg - (negative)
Anti Hbe positive
Anti Hbc IGM : Negative
Anti Hbc Total (serum) : positive
HBV DNA (quantitative) :-
409261 IU/ml
2169083.3 copies/ml
My liver function test are normal...
I'm confused on why my viral load is high...
Can someone explain my situation??
Going to do a fibroscan on Monday
My results are :-
HbsAg + (reactive)
HbeAg - (negative)
Anti Hbe positive
Anti Hbc IGM : Negative
Anti Hbc Total (serum) : positive
HBV DNA (quantitative) :-
409261 IU/ml
2169083.3 copies/ml
My liver function test are normal...
I'm confused on why my viral load is high...
Can someone explain my situation??
Going to do a fibroscan on Monday
It makes sense, if this process continues, that relatively more hbsag than virion dna are produced. Since the integration process grows with time, an old E antigen negative patient is likely to have more integration and hence non cccDNA produced hbsag.
The arrowhead results , as shown in late 2015 have brought this painfully to light. Since their drug only reduces hbsag from cccDNA, the suppression was only 30% in these patients.
since the arrowhead results were public, will guidelines change now for hbeag + patients. would we treat immediately in hbeag + patients to lower dna and hbsag and combine with peg for chance of clearance? also if we treat right away in hbeag + , do they acquire mutations when seroconvert to hbeag -?
The arrowhead results , as shown in late 2015 have brought this painfully to light. Since their drug only reduces hbsag from cccDNA, the suppression was only 30% in these patients.
since the arrowhead results were public, will guidelines change now for hbeag + patients. would we treat immediately in hbeag + patients to lower dna and hbsag and combine with peg for chance of clearance? also if we treat right away in hbeag + , do they acquire mutations when seroconvert to hbeag -?
The hbsag is in the medium range, but a little high for dna neg.
Mike.. your hbsag to dna situation is good, as described above. Easy to sericonvert, theoretically even lesser chances for hcc.
Mike.. your hbsag to dna situation is good, as described above. Easy to sericonvert, theoretically even lesser chances for hcc.
My HBsAg is 4400 iu/ml. Undetectable viral load..no treatment.Does this quantity is higher or its in medium limit or lower?
1 Comments
Thanks studyforhope. HBsAg 4400 iu/ml, is it like it will never decrease and seroconverted or there are certain chances that it will be serovonverted without any treatment? I am sure that I got this virus 4-5 years back and wondering why HBsag is so high for HBsAg negative with undetectable viral load.
Mutations effecting intensity of hbsag or virion production can be numerous, the standard bcp and pc mutations are involved also but not at the center of this effect.
In most Hbeag pos patients the linear relationship should hold reasonable well, on the way to long standing e neg infection integration and adaptive mutation will get more prevalent.
It is a better situation to have a lower hbsag level, since the chance to seroconvert to hbsag neg and hbsag antibody positive are obviously better.
if you can't have an antibody, it is h ARD to prevent reinfection, no matter what you did to reduce cccDNA.
In most Hbeag pos patients the linear relationship should hold reasonable well, on the way to long standing e neg infection integration and adaptive mutation will get more prevalent.
It is a better situation to have a lower hbsag level, since the chance to seroconvert to hbsag neg and hbsag antibody positive are obviously better.
if you can't have an antibody, it is h ARD to prevent reinfection, no matter what you did to reduce cccDNA.
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So in my So in my situation with high dna but low hbsag. Is it considered better than having low dna and high hbsag? Which one is more likely to mutate and harm your liver etc....situation with high dna but low hbsag. Is it considered better than having low dna and high hbsag? Which one is more likely to mutate and harm your liver etc....
Studyforhope.....Thanks Studyforhope so much. So, if someone has high hbsag but low DNA this could be either from integrated DNA and/or mutations? Are these mutations the typical precore, core promoter that are commonly tested or other mutations that are not available in commercial labs?
For most of us, do DNA and hbsag usually parallel each other fairly well, or is this inverse relationship quite common for HbeAg negative?
I know we can't pick but if we do have that inverse relationship is it a better situation to have high hbsag/low DNA or better to have low hbsag/high DNA? The reason I ask is because everything in the US revolves around DNA but here on medhelp we know low hbsag is key to immune control and possible hbsag loss, correct?
For most of us, do DNA and hbsag usually parallel each other fairly well, or is this inverse relationship quite common for HbeAg negative?
I know we can't pick but if we do have that inverse relationship is it a better situation to have high hbsag/low DNA or better to have low hbsag/high DNA? The reason I ask is because everything in the US revolves around DNA but here on medhelp we know low hbsag is key to immune control and possible hbsag loss, correct?
Treatment with antivirals will reduce inflammation and have a positive influence on hcc development. HBsAg production from integrated dna will not be affected by that.
Naps will have some effect on integration by increasing immune efficacy, possibly eliminating some cells with hbsag production only by class I tcell action on hbsag epitopes. But the efficacy of this is likely fairly low.
once naps are stopped the integrated hbsag gene will be able to secret particles again, removing the antibody excess by complexing.
birinapant seemed to be ideally positioned to eliminate those cells, but it's development is quite in doubt.
Peg ifn or Zadaxin in combo with naps will work much bette than naps alone, but results after ending treatment long term remain to be seen.
Ultrasound monitoring for hcc is always important, single cancers can be curative removed if detected early.
Naps will have some effect on integration by increasing immune efficacy, possibly eliminating some cells with hbsag production only by class I tcell action on hbsag epitopes. But the efficacy of this is likely fairly low.
once naps are stopped the integrated hbsag gene will be able to secret particles again, removing the antibody excess by complexing.
birinapant seemed to be ideally positioned to eliminate those cells, but it's development is quite in doubt.
Peg ifn or Zadaxin in combo with naps will work much bette than naps alone, but results after ending treatment long term remain to be seen.
Ultrasound monitoring for hcc is always important, single cancers can be curative removed if detected early.
I am not aware of such a study, but it might well exist. There is little doubt, that a high degree of integration is a risk factor for hcc, but it might be an early one and correlations are hard to assess due to all the additional factoes that are needed to actually promote a cancer development.
Oops Pressed the "post" buttom to early
Treatment? Just monitoring? Or something that maybe in the pipeline may offer more favourable results?
(Just for speculating)
Treatment? Just monitoring? Or something that maybe in the pipeline may offer more favourable results?
(Just for speculating)
As the case you described whats your thoughts (from a speculating view point)
On how to tackle the infection with the duel factor in mind?
Treatment or just monitor?
On how to tackle the infection with the duel factor in mind?
Treatment or just monitor?
Thanks studyforhope. Is there any study which links low viral load and high HBsAg to risk of HCC or cirrhosis or prognosis? Less, more or medium??
When the infection starts, the cccDNA is the only template from which both virions and hbsag are synthesized through a serious of steps, many for for the virion synthesis however, due to the multiple components and complex mechanics of final dna synthesis.
Therefore in a standard situation, the total amount of cccDNA is proportional to both hbsag and virion production, as has indeed been shown many times.
When high amounts of viral dna synthesis are combined with hepatocyte replication , particular under inflammatory stress, then an increasing amount of hbv dna becomes integrated into the human chromosomes at various places. We called this here integrated hbv dna and it is normally not able to produce virions from these viral genes embedded in our chromosomes but mainly hbsag.
now the hbsag has two sources, the cccDNA and the integrated hbv dna.
It makes sense, if this process continues, that relatively more hbsag than virion dna are produced. Since the integration process grows with time, an old E antigen negative patient is likely to have more integration and hence non cccDNA produced hbsag.
The arrowhead results , as shown in late 2015 have brought this painfully to light. Since their drug only reduces hbsag from cccDNA, the suppression was only 30% in these patients.
Thus in situations where untreated a low dna and a high hbsag are found we must suspect a substantial amount of integration.
There are however other possible reason for nonparallelity of hbsag and hbv dna.
each gene expression intensity is controlled by a promoter region and also transcription enhancers. Mutations in these could preferentially affect hbsag or virion component transcription, explaining a divergence in both directions.
Lastly, the blocking effect of Tcells operating through cytokines could affect the production steps for hbsag and virions differently, again leading to a divergence of final product amounts as secreted into the bloodstream.
Therefore in a standard situation, the total amount of cccDNA is proportional to both hbsag and virion production, as has indeed been shown many times.
When high amounts of viral dna synthesis are combined with hepatocyte replication , particular under inflammatory stress, then an increasing amount of hbv dna becomes integrated into the human chromosomes at various places. We called this here integrated hbv dna and it is normally not able to produce virions from these viral genes embedded in our chromosomes but mainly hbsag.
now the hbsag has two sources, the cccDNA and the integrated hbv dna.
It makes sense, if this process continues, that relatively more hbsag than virion dna are produced. Since the integration process grows with time, an old E antigen negative patient is likely to have more integration and hence non cccDNA produced hbsag.
The arrowhead results , as shown in late 2015 have brought this painfully to light. Since their drug only reduces hbsag from cccDNA, the suppression was only 30% in these patients.
Thus in situations where untreated a low dna and a high hbsag are found we must suspect a substantial amount of integration.
There are however other possible reason for nonparallelity of hbsag and hbv dna.
each gene expression intensity is controlled by a promoter region and also transcription enhancers. Mutations in these could preferentially affect hbsag or virion component transcription, explaining a divergence in both directions.
Lastly, the blocking effect of Tcells operating through cytokines could affect the production steps for hbsag and virions differently, again leading to a divergence of final product amounts as secreted into the bloodstream.
I am not on any medication so far.My HBsAg is 4400 iu/ml and undetectable viral load. All other things are normal.I really don't know I am active or inactive. After 3.5 years of marriage my wife didn't get HBV from me although she was not protected!!
This is an jnteresting topic because im one of those cases. My hbeag dna is between 2000 and 9000 iu/ml. While my hbsag is 150 iu/ml
So active or inactive? I wonder since im in no medication and my liver seems low on fibroscan 4.8 but little coarsened on ultrasound.
It is hard to say and like professor LOk told me that im in the grey area. Not inactive but really not active :)
So active or inactive? I wonder since im in no medication and my liver seems low on fibroscan 4.8 but little coarsened on ultrasound.
It is hard to say and like professor LOk told me that im in the grey area. Not inactive but really not active :)
1 Comments
I thought of you when trying to figure out this situation Mike. :)
Before the answer can be given, the basic view of the viral system and its propagation has to be clarified.
if you use the terms dna and hbsag I assume you mean the quantity of these two hbv related substances in the peripheral blood, where the test material is obtained?
If yes then I assume you are aware that the dna is indeed a quantity of hbv dna determined, but that this dna is extracted from lysed virions in the test procedure and the placed into a directly measurable range by PCR amplification?
and hbsag refers to the quantity of subviral particle spheres that also circulate in the blood?
if you use the terms dna and hbsag I assume you mean the quantity of these two hbv related substances in the peripheral blood, where the test material is obtained?
If yes then I assume you are aware that the dna is indeed a quantity of hbv dna determined, but that this dna is extracted from lysed virions in the test procedure and the placed into a directly measurable range by PCR amplification?
and hbsag refers to the quantity of subviral particle spheres that also circulate in the blood?
1 Comments
Yes, I am referring to the quantification of the hbsag and the DNA. Mike9111, RAM1982, and others are a perfect example of these inverse relationships between DNA PCR and hbsag quant that I'm wondering the cause of this discrepancy. Thank you.
"From what I can make of it, the DNA does not come from infected cells but from new virions being infected, which tell how active or inactive the virus is."
Can you Pls elaborate on this statement, rephrase it maybe?
Can you Pls elaborate on this statement, rephrase it maybe?
1 Comments
I guess what it comes down to is that I have a hard time really understanding the difference between hbsag and DNA, and I was trying my best to lay out my understanding, which may very well be wrong.
Bottom line, for hbeag negative i do not understand why some have high hbsag but low DNA (no nucs) and why others can have the opposite. I know some have high both and others low both, but don't understand why some have the inverse. Are hbsag and DNA totally unrelated? I hope I don't sound like a complete idiot. Haha.
Bottom line, for hbeag negative i do not understand why some have high hbsag but low DNA (no nucs) and why others can have the opposite. I know some have high both and others low both, but don't understand why some have the inverse. Are hbsag and DNA totally unrelated? I hope I don't sound like a complete idiot. Haha.
Just my opinion
Keeping in mind each one of us is unique and there are many variables.
However hbsag doesnt do the damage thats correct its actually our immune that does the damage trying to clear the virus.
I guess there needs to be considerations when a shift to immune tolerant stage as to the "state of play" so to speak as unmanaged/unmonitered viral loads can go up and down by considerable amounts in short periods.Yet dependant on how many cells its intergrated aswell as I said many variables. just my opinion.
Keeping in mind each one of us is unique and there are many variables.
However hbsag doesnt do the damage thats correct its actually our immune that does the damage trying to clear the virus.
I guess there needs to be considerations when a shift to immune tolerant stage as to the "state of play" so to speak as unmanaged/unmonitered viral loads can go up and down by considerable amounts in short periods.Yet dependant on how many cells its intergrated aswell as I said many variables. just my opinion.
I've been reading past threads and would like to know if my train of thought is on the right track. Studyforhope or Stephen please let me know.
From what I can make of it, the DNA does not come from infected cells but from new virions being infected, which tell how active or inactive the virus is.
Hbsag comes from how many infected cells there are in the liver. Dos this come from when one moves from the immune tolerant to immune clearance phase, or is it a continuous new production of infected cells?
Is there a correlation between the two or are they totally separate things?
Can we assume if hbsag is low and DNA low we do not cause damage to the liver (aside from knowing the cccdna integration), since from what I read hbsag on its own does not produce damage?
Thank you!
From what I can make of it, the DNA does not come from infected cells but from new virions being infected, which tell how active or inactive the virus is.
Hbsag comes from how many infected cells there are in the liver. Dos this come from when one moves from the immune tolerant to immune clearance phase, or is it a continuous new production of infected cells?
Is there a correlation between the two or are they totally separate things?
Can we assume if hbsag is low and DNA low we do not cause damage to the liver (aside from knowing the cccdna integration), since from what I read hbsag on its own does not produce damage?
Thank you!
This was just a question based on others situations, not mine, as we can't even get quant hbsag quant in the US. :)
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